The main features of velo-cardio-facial syndrome are cleft palate, typical facies, heart defects and specific learning difficulties. Hemizygosity within human chromosome (Chr) 22q11 has been associated with several human congenital defects, among them velo-cardio-facial syndrome (VCFS), DiGeorge syndrome (DGS), conotruncal anomaly face syndrome and familial congenital heart disease. The spectrum of anomalies in VcFS has prompted attention to a phenotypic overlap between VCFS and the DiGeorge sequence. A recent study carried out by the Center for Craniofacial Disorders at Montefiore Medical Center confirms that the genes involved in VCFS and DGS are closely linked and may be identical. Importantly not only are microdeletions of 22q11 associated with VCFS/DGS, but patients that are partially trisomy for this region (supernumerary 22 syndrome) have similar phenotypes, suggesting gene dosage is an underlying factor. Pathogenesis of features and chromosomal homologous regions shared by mice that are trisomy 16 (TS16) and Down Syndrome (TS 21) individuals have been a basis for the TS 16 mouse being a model system for studies related to Down Syndrome. Our echocardiography results on heart anomalies of full TS 16 mice and partial TS16 mice suggested that the TS16 mice may be a better model for VCF/DGS than for Down Syndrome. More recently a gene expressed during early embryogenesis from the 22q11 commonly deleted region in DGS is shown to map to mouse Chr16. The aims of this grant application are:(1)To isolate two mouse cDNA probes that are homologous to those reported to map to the commonly deleted region in DOS in the human. (2) To use these probes to carry out in situ hybridization studies of the first and second pharyngeal arch region and of the developing palate region between days 11-13 of gestation in the trisomic 16 mouse in comparison to normal litter mates that serve as controls. This will allow assessing specific cDNA probes for their involvement in developmental processes that may lead to cleft or normal palate development. (3) To address the possibility of utilizing a reciprocal translocation T(15;16)6ODn which produces segmental trisomy for the proximal end of Chr 16 to produce a trisomic mouse model for the VCF/DG chromosomal region to analyze dosage effects. These studies provide a basis for future analyses related to functionality of the genes that become identified as important to palate and orofacial development.